The present application proposes to continue our in vivo ultrastructural studies on the cellular mechanisms by which the rabbit ductus arteriosus (DA) wall reorganizes its structure prior to closure. This reorganization results in an intimal thickening which seems to make a significant contribution to the ultimate closure of the DA lumen. The cellular events involved include medial smooth muscle cell (SMC) reorientation and apparent migration into the intima. In addition, these and other cellular aspects of DA closure are very similar to critical events occurring in the adult human arterial wall during the early pathogenesis of intimal fibromuscular lesions (IFML), and closure of the DA serves as a convenient natural model of basic aspects of IFML formation. Our goals are: 1) to perform quantitative scanning electron microscopic studies on the endothelial contraction which immediately precedes DA closure, the formation of ghost bodies by underlying SMC, and the effects of indomethacin on such events, 2) to describe and quantitate by light and transmission electron microscopy the necrosis of the inner DA wall SMC after DA closure and determine if lack of circulation is the sole cause, and 3) to study the effects of functional denervation through impaired axonal transport, caused by vinblastine dispensing osmotic pumps, on the reorganization and closure of the DA. It is hoped that these studies will lead to a better understanding of factors controlling the cellular mechanisms involved in beneficial closure of the DA. This new understanding may result in a more efficient means of preventing the occurrence of both patent DA in the human infant and occlusive IFML formation in adult arteries.